Biology subjects

Chevreau, R.

Publications and source records attributed to Chevreau, R..

3 recordsLinked to original sources

bioRxiv2024

Arf family GTPases are present in Asgard archaea

The emergence of eukaryotes from their prokaryotic ancestors is one of the most fundamental evolutionary events in the history of life. Little is robustly known about how eukaryogenesis occurred, but a major breakthrough came with the identification of the Asgardarchaeota, the closest prokaryotic lineage to eukaryotes yet discovered. Endomembrane organelles, and the capacity to transport material between them, are major hallmarks of eukaryotic cells. The Arf family GTPases are crucial regulators of organelle dynamics in eukaryotes, functioning in vesicle budding, membrane tethering and membrane-cytoskeleton interactions. Although an expanded GTPase complement has been reported in the Asgardarchaeota, the specific origins of the Arf family remain elusive. Here we report a new group of prokaryotic GTPases, the ArfRs. Widely present in Asgardarchaeota and almost exclusive to them, it is the clade from which all eukaryotic Arf family proteins are derived. Heterologous expression of representative Asgardarchaeota ArfR proteins in the model eukaryote Saccharomyces cerevisiae and X-ray crystallographic studies demonstrate that ArfR GTPases possess the mechanism of membrane binding and structural features unique to Arf family proteins. Our results show that Arf family GTPases are present in Asgardarchaeota, and strongly suggest that they originated in the archaeal contributor to eukaryogenesis, providing support for nascent endomembrane system capacity evolving early in eukaryogenesis.

evolutionary biology↗

bioRxiv2022

Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord

Spinal cord ependymal cells have stem cell properties in mice. They surround the central canal and keep expressing spinal cord developmental transcription factors. Similar cells exist in young humans however their persistence with aging is debated. We clarified this issue by collecting 17 spinal cords from organ donors, aged between 37 and 83 years old. We examined the presence of ependymal cells using immunohistochemistry on lightly-fixed tissue. We found the presence of cells expressing the typical ependymal marker FOXJ1 in the spinal cord central region in 100% of cases. In addition, a lumen surrounded by FOXJ1+ cells was observed in half of the cases. Like in mice, these human ependymal cells maintain the expression of SOX2 and PAX6 proteins together with RFX2 a master transcriptional regulator of ciliogenesis and ARL13B, a regulatory GTPase enriched in cilia. Reminiscent of the situation observed in mice and in young human spinal cord, a fetal-like regionalization of neurodevelopmental transcription factors was observed in three donors aged over 75 years: MSX1 and ARX/FOXA2 was preferentially expressed by dorsal and ventral ependymal cells, respectively. These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life. The persistence of these cells in humans opens new opportunities to regenerate the spinal cord.

neuroscience↗

bioRxiv2021

Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells

Ependymal cells with stem cell properties reside in the adult spinal cord around the central canal. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, six of them more than 20 fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr. OSMR is the receptor for the inflammatory cytokine oncostatin (OSM) and we studied its regulation and role using neurospheres derived from ependymal cells. We found that OSM induces strong OSMR and p-STAT3 expression together with proliferation reduction and astrocytic differentiation. Conversely, production of oligodendrocyte-lineage OLIG1+ cells was reduced. OSM is specifically expressed by microglial cells and was strongly upregulated after injury. We observed microglial cells apposed to ependymal cells in vivo and co-cultures experiments showed that these cells upregulate OSMR in neurosphere cells. Collectively, these results support the notion that microglial cells and OSMR/OSM pathway regulate ependymal cells in injury. In addition, the generated high throughput data provides a unique molecular resource to study how ependymal cell react to spinal cord lesion.

cell biology↗